The mechanism of movement instrumental learning in a Hopfield environment in the feline motor cortex

A model of the neuronal processes in the motor cortex is proposed, which provides the mechanism for instrumentalization (voluntary reproduction) of movements primarily evoked by stimulation of the parietal cortex. The main propositions of the model are as follows: the late NMDA-dependent response of the motor cortex neurons to stimulation of the parietal cortex reflects the discharges in the recurrent collaterals of the pyramidal cell axons; learning processes in the motor cortex are based on the long-term potentiation of the efficiency of the recurrent collaterals; the Hopfield's theory of neuronal nets is applied to the processes of motor learning in the cortex. The movement instrumentalization is viewed as the stable state formation in the collaterally linked neuronal structure; the voluntary reproduction of the previously learned movement in considered as the process of transition of the neuronal structure into the stable state. The data on acetylcholine and dopamine modulatory influences on the reactions of motor cortex neurons are discussed.     

Experimental study with radiofrequency-induced thermal arterial occlusion

Intraspinal replantation of avulsed spinal nerve roots as a surgical treatment for motor deficits after severe brachial plexus injury was investigated in primates. Under general anaesthesia hemi-laminectomy was performed in cynomolgus monkeys (Macaca fascicularis). Ventral roots within the brachial plexus were then avulsed by traction and subsequently implanted into the ventrolateral aspect of the spinal cord. No dysfunction in the long fibre tracts was seen following surgery. Postoperatively there was a flaccid paralysis of the arm on the lesioned side. Severe atrophy developed within 5-7 weeks in the muscles supplied by the avulsed roots and EMG revealed denervation activity. Two to three months after surgery there were EMG signs of reinnervation, which were shortly followed by evidence of clinical recovery. A gradual improvement in the function of the affected arm occurred and the animals' motor behaviour normalised. One year after surgery there was a full range of motion in the arm, but the EMG activity in the reinnervated muscles at maximal force was reduced. Tracing of regenerated motor neurons with horseradish peroxidase (HRP) injected into the biceps muscle revealed retrogradely labelled motor neurons confined to the ipsilateral ventral horn. It was concluded that intraspinal replantation of avulsed ventral roots in primates significantly promotes motor recovery in the muscles supplied by the lesioned spinal cord segments.     

Precentral glioma location determines the displacement of cortical hand representation

OBJECTIVE: Low-grade brain tumors may remain asymptomatic in contrast to malignant gliomas. The mechanisms underlying the preservation of cerebral function in such gliomas are not well understood. METHODS: We used positron emission tomography and transcranial magnetic stimulation for presurgical monitoring of motor hand function in six patients with gliomas of the precentral gyrus. All patients were able to perform finger movements of the contralesional hand. RESULTS: Movement-related increases of the regional cerebral blood flow occurred only outside the tumor in surrounding brain tissue. Compared with the contralateral side, these activations were shifted by 20 +/- 13 mm (standard deviation) within the dorsoventral dimension of the precentral gyrus. This shift of cortical hand representation could not be explained by the deformation of the central sulcus as determined from the spatially aligned magnetic resonance images but was closely related to the location of the maximal tumor growth. Dorsal tumor growth resulted in ventral displacement of motor hand representation, leaving the motor cortical output system unaffected, whereas ventral tumor growth leading to dorsal displacement of motor hand representation compromised the motor cortical output, as evident from transcranial magnetic stimulation. In two patients, additional activation of the supplementary motor area was present. CONCLUSION: Our data provide evidence for the reorganization of the human motor cortex to allow for preserved hand function in Grade II astrocytomas.     

The cognitive and neural architecture of sequence representation.

The authors theorize that 2 neurocognitive sequence-learning systems can be distinguished in serial reaction time experiments, one dorsal (parietal and supplementary motor cortex) and the other ventral (temporal and lateral prefrontal cortex). Dorsal system learning is implicit and associates noncategorized stimuli within dimensional modules. Ventral system learning can be implicit or explicit. It also allows associating events across dimensions and therefore is the basis of cross-task integration or interference, depending on degree of cross-task correlation of signals. Accordingly, lack of correlation rather than limited capacity is responsible for dual-task effects on learning. The theory is relevant to issues of attentional effects on learning; the representational basis of complex, sequential skills; hippocampal- versus basal ganglia-based learning; procedural versus declarative memory; and implicit versus explicit memory. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

GABA-receptor-independent dorsal root afferents depolarization in the neonatal rat spinal cord

Dorsal root afferent depolarization and antidromic firing were studied in isolated spinal cords of neonatal rats. Spontaneous firing accompanied by occasional bursts could be recorded from most dorsal roots in the majority of the cords. The afferent bursts were enhanced after elevation of the extracellular potassium concentration ([K+]e) by 1-2 mM. More substantial afferent bursts were produced when the cords were isolated with intact brain stems. Rhythmic afferent bursts could be recorded from dorsal roots in some of the cords during motor rhythm induced by bath-applied serotonin and N-methyl--aspartate (NMDA). Bilaterally synchronous afferent bursts were produced in pairs of dorsal roots after replacing the NaCl in the perfusate with sodium-2-hydroxyethansulfonate or after application of the gamma-aminobutyric acid-A (GABAA) receptor antagonist bicuculline with or without serotonin (5-HT) and NMDA. Antidromic afferent bursts also could be elicited under these conditions by stimulation of adjacent dorsal roots, ventrolateral funiculus axons, or ventral white commissural (VWC) fibers. The antidromic bursts were superimposed on prolonged dorsal root potentials (DRPs) and accompanied by a prolonged increase in intraspinal afferent excitability. Surgical manipulations of the cord revealed that afferent firing in the presence of bicuculline persisted in the hemicords after hemisection and still was observed after removal of their ventral horns. Cutting the VWC throughout its length did not perturb the bilateral synchronicity of the discharge. These findings suggest that the activity of dorsal horn neurons is sufficient to produce the discharge and that the bilateral synchronicity can be maintained by cross connectivity that is relayed from side to side dorsal to the VWC. Antagonists of GABAB, 5-HT2/5-HT1C, or glutamate metabotropic group II and III receptors could not abolish afferent depolarization in the presence of bicuculline. Depolarization comparable in amplitude to DRPs, could be produced in tetrodotoxin-treated cords by elevation of [K+]e to the levels reported to develop in the neonatal rat spinal cord in response to dorsal root stimulation. A mechanism involving potassium transients produced by neuronal activity therefore is suggested to be the major cause of the GABA-independent afferent depolarization reported in our study. Possible implications of potassium transients in the developing and the adult mammalian spinal cord are discussed.     

Effects of hippocampal N-methyl-[D]-aspartate infusion on locomotor activity and prepulse inhibition: Differences between the dorsal and ventral hippocampus.

Prepulse inhibition (PPI) of the acoustic startle response and open-field locomotor activity were measured after bilateral infusion of N-methyl-[D]-aspartate into the ventral (0.10, 0.25, 0.50 Ag/side) and dorsal (0.10, 0.25, 0.50, 0.70 wg/side) hippocampus of Wistar rats. Dose-dependent hyperactivity and disruption of PPI-behavioral effects related to psychotic symptoms-were observed after ventral infusions but were virtually absent after dorsal infusions. This functional dorsal-ventral difference might be related to the different connections of the dorsal and ventral hippocampus with the amygdala, nucleus accumbens, and prefrontal cortex, which have been implicated in the regulation of locomotor activity and PPI. Hippocampal overactivity has been associated with schizophrenia. The findings suggest that overstimulation of the ventral hippocampal projections may contribute to behavioral outcomes related to psychotic symptoms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modulation of plasticity in human motor cortex after forearm ischemic nerve block

Deafferentation leads to cortical reorganization that may be functionally beneficial or maladaptive. Therefore, we were interested in learning whether it is possible to purposely modulate deafferentation-induced reorganization. Transient forearm deafferentation was induced by ischemic nerve block (INB) in healthy volunteers. The following five interventions were tested: INB alone; INB plus low-frequency (0.1 Hz) repetitive transcranial magnetic stimulation of the motor cortex ipsilateral to INB (INB+rTMSi); rTMSi alone; INB plus rTMS of the motor cortex contralateral to INB (INB+rTMSc); and rTMSc alone. Plastic changes in the motor cortex contralateral to deafferentation were probed with TMS, measuring motor threshold (MT), motor evoked-potential (MEP) size, and intracortical inhibition (ICI) and facilitation (ICF) to the biceps brachii muscle proximal to the level of deafferentation. INB alone induced a moderate increase in MEP size, which was significantly enhanced by INB+rTMSc but blocked by INB+rTMSi. INB alone had no effect on ICI or ICF, whereas INB+rTMSc reduced ICI and increased ICF, and conversely, INB+rTMSi deepened ICI and suppressed ICF. rTMSi and rTMSc alone were ineffective in changing any of these parameters. These findings indicate that the deafferented motor cortex becomes modifiable by inputs that are normally subthreshold for inducing changes in excitability. The deafferentation-induced plastic changes can be up-regulated by direct stimulation of the "plastic" cortex and likely via inhibitory projections down-regulated by stimulation of the opposite cortex. This modulation of cortical plasticity by noninvasive means might be used to facilitate plasticity when it is primarily beneficial or to suppress it when it is predominately maladaptive.     

Responses of neurons of the first and second somatosensory zones of the cortex to peripheral, thalamic and cortical stimulation

Experiments were performed on cats immobilized with d-tubocurarine or myorelaxin. Neuronal responses were studied in the first somatosensory cortex (SI) to the second somatosensory cortex (SII), ventroposterior nucleus (VP) and contralateral forepaw stimulation. Besides, neuronal responses in SII to SI, VP and contralateral forepaw stimulation were also studied. It was shown that in SII the percentage of neurons excited by afferent volley with two or more synaptic change-overs in the cerebral cortex was larger than in SI. Neurons of SI and SII responded to cortical stimulation ortho- and antidromically, thus confirming the existence of bilateral cortico-cortical connections. Both in SI and SII, PSPs to cortical stimulation were similar in character to PSPs in the same neurons to VP stimulation. In 50.0% of SI neurons and 37.1 of SII neurons the difference in latencies of orthodromic spike potentials to VP and cortical stimulation was less than 1.0 ms. In 19.6% of SI neurons and 41.4% of SII neurons the latency of the response to cortical stimulation was 1.6-4.7 ms shorter than that of the response in the same neuron to VP stimulation. It is supposed that impulses from SI participate significantly in afferent activation of SII neurons.     

Modulation of outer hair cell compliance and force by agents that affect hearing

Electrical stimulation of area infraradiata in the rat evokes transient changes in arterial pressure, but the locations that evoke these responses have not been mapped by neurochemical methods. To localize more specifically the regions of area infraradiata that modify cardiovascular activity, the present study measured cardiovascular responses to localized chemical stimulation of neurons in area infraradiata of urethane-anesthetized rats (n = 21). Microinjections (50-200 nl) of the glutamate agonist D,L-homocysteic acid into area infraradiata evoked both increases and decreases in arterial pressure and heart rate. Injections in the ventral subdivisions of rostral area infraradiata (IRa alpha and IRb alpha) produced cardiovascular responses with the highest probability and greatest magnitude. Of 53 injections in this area, 18 decreased arterial pressure and heart rate, whereas 4 increased arterial pressure and heart rate. In contrast to the results from the ventral subdivision of rostral infraradiata cortex, injections of D,L-homocysteic acid in the dorsal subdivision of rostral infraradiata cortex (IRc alpha) or any of the caudal subdivisions of area infraradiata (IR beta) produced less consistent changes in arterial pressure. To demonstrate that the general anesthesia did not significantly alter the evoked responses in this study, similar injections of D,L-homocysteic acid were made into area infraradiata of unrestrained, conscious rats (n = 10) and the responses were similar to the responses evoked in urethane-anesthetized rats. These results indicate that the ventral subdivisions of rostral area infraradiata (IRa alpha and IRb alpha) are more involved in cardiovascular regulation than other areas of infraradiata cortex (IRc alpha and IR beta), and that both pressor and depressor sites are present in both areas.     

Functional anatomy of pointing and grasping in humans

The functional anatomy of reaching and grasping simple objects was determined in nine healthy subjects with positron emission tomography imaging of regional cerebral blood flow (rCBF). In a prehension (grasping) task, subjects reached and grasped illuminated cylindrical objects with their right hand. In a pointing task, subjects reached and pointed over the same targets. In a control condition subjects looked at the targets. Both movement tasks increased activity in a distributed set of cortical and subcortical sites: contralateral motor, premotor, ventral supplementary motor area (SMA), cingulate, superior parietal, and dorsal occipital cortex. Cortical areas including cuneate and dorsal occipital cortex were more extensively activated than ventral occipital or temporal pathways. The left parietal operculum (putative SII) was recruited during grasping but not pointing. Blood flow changes were individually localized with respect to local cortical anatomy using sulcal landmarks. Consistent anatomic landmarks from MRI scans could be identified to locate sensorimotor, ventral SMA, and SII blood flow increases. The time required to complete individual movements and the amount of movement made during imaging correlated positively with the magnitude of rCBF increases during grasping in the contralateral inferior sensorimotor, cingulate, and ipsilateral inferior temporal cortex, and bilateral anterior cerebellum. This functional-anatomic study defines a cortical system for "pragmatic' manipulation of simple neutral objects.     

Long-term potentiation of the neuronal activity in the motor cortex induced by simultaneous stimulation of the thalamus and somatosensory cortex in cats

Long-lasting potentiation of the cat motor cortex units induced by tetanic stimulation of the VL + SCx led to an increase of the motor cortex unit discharge rate. The findings suggest that co-activation of cortico-cortical and thalamo-cortical afferents modifies neuronal activity of the motor cortex at the specific site which receives convergent sensory input from the thalamus and the somatosensory cortex.     

A phylogenetic assessment of the eukaryotic light-harvesting antenna proteins, with implications for plastid evolution

Stimulation of cutaneous foot afferents has been shown to evoke a facilitation of the tibialis anterior (TA) EMG-activity at a latency of 70-95 ms in the early and middle swing phase of human walking. The present study investigated the underlying mechanism for this facilitation. In those subjects in whom it was possible to elicit a reflex during tonic dorsiflexion while seated (6 out of 17 tested), the facilitation in the TA EMG evoked by stimulation of the sural nerve (3 shocks, 3-ms interval, 2.0-2.5x perception threshold) was found to have the same latency in the swing phase of walking. The facilitation observed during tonic dorsiflexion has been suggested to be -- at least partly -- mediated by a transcortical pathway. To investigate whether a similar mechanism contributes to the facilitation observed during walking, magnetic stimulation of the motor cortex (1.2x motor threshold) was applied in the early swing phase at different intervals in relation to the cutaneous stimulation in 17 subjects. In 13 of the subjects, the motor potentials evoked by the magnetic stimulation (MEPs) were more facilitated by prior sural-nerve stimulation (conditioning-test intervals of 50-80 ms) than the algebraic sum of the control MEP and the cutaneous facilitation in the EMG when evoked separately. In four of these subjects, a tibialis anterior H-reflex could also be evoked during walking. In none of the subjects was an increase of the H-reflex similar to that for the MEP observed. In five experiments on four subjects, MEPs evoked by magnetic and electrical cortical stimulation were compared. In four of these experiments, only the magnetically induced MEPs were facilitated by prior stimulation of the sural nerve. We suggest that a transcortical pathway may also contribute to late cutaneous reflexes during walking.     

Delayed development of spontaneous seizures and prolonged convulsive state in rats after massed stimulation of the anterior piriform cortex

We studied the short- and long-term epileptogenic effects of massed stimulation (MS) of the piriform cortex. Sprague-Dawley rats with electrodes implanted bilaterally in the anterior piriform cortex and the dorsal and ventral hippocampi underwent MS: electrical stimulation of the left piriform cortex every 5 min for 6 h (afterdischarge threshold, 60 Hz, 1 ms, 1 s). Animals were retested (5 stimulations) 3-4 times later at different time points to check for the kindled state. Our data showed that MS resulted in delayed development of severe epilepsy. The interval between MS and the first appearance of convulsive response (2 weeks) was characterized by deep refractoriness to seizure (silent period). Unexpectedly, dramatic seizure activity occurred 4-7 weeks after MS. This was manifested by (1) generalized tonic-clonic convulsions with multiple failings, which were elicited repeatedly during retest; (2) frequent progression of elicited generalized convulsions into a prolonged (> 8 min) postictal convulsive state expressed mainly by continuous partial seizures and even new bouts of generalized seizures, and (3) development of mild spontaneous seizures. We found that epileptiform activity predominated in the ventral hippocampus. Mossy fiber sprouting was also most pronounced in this area. We propose that the MS resulted in formation of pathological circuits which involve both piriform cortex and ventral hippocampus and lead to severe epilepsy.     

Dissociating ventral and dorsal subicular dopamine D? receptor involvement in instrumental learning, spontaneous motor behavior, and motivation.

A series of experiments investigating the role of dopamine D? receptors in the ventral subiculum (vSUB) and dorsal subiculum (dSUB), 2 subregions of the hippocampal formation, found that D? receptor antagonism (3.0 nmol/0.5 μl SCH-23390 bilaterally) in the vSUB impaired instrumental learning and performance, reduced break point in progressive ratio (PR) tests, and produced an intrasession decline in responding during test sessions, but had no effect on spontaneous motor or food-directed behavior. In contrast, D? receptor blockade in the dSUB had no effect on instrumental learning, performance, PR break point, or food-directed behavior, but reduced spontaneous motor behavior. These results suggest a dissociation between the vSUB and dSUB with respect to the role of dopamine in various aspects of motivated and motor behavior. Further, D? activation in the vSUB may be a critical component of motivational arousal associated with learned contextual cues. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rapid rate transcranial magnetic stimulation--a safety study

We assessed the safety of repeated short trains (4 stimuli) of rapid-rate transcranial magnetic stimulation (rrTMS) over the left motor cortex in 6 healthy normal subjects. rrTMS involved two separate blocks of 50 consecutive trains of 4 stimuli at a frequency of 20 Hz and an intensity of 5-10% above active motor threshold. We monitored EEG, and assessed aspects of neurological (balance, gait, two-point discrimination, blood pressure, pulse rate), cognitive (attention, memory, executive function) and motor function (speed of movement initiation and execution and manual dexterity) before and after the two blocks of rrTMS. EMG was also recorded from a number of hand, forearm and arm muscles contralateral to the site of stimulation. Two blocks of repeated rrTMS at 20 Hz and 5-10% above active motor threshold did not produce any adverse effects. Measures of neurological, cognitive and motor function showed no change following rrTMS. From the EMG recording there was evidence of increase in the amplitude of the motor evoked potentials (MEPs) recorded from the biceps in one subject during the first block of rrTMS, but this did not occur in the second block. A similar magnification of MEPs was also observed in another subject only during the second block of stimulation. When applied using parameters falling within published guidelines (Pascual-Leone et al., 1993; Pascual-Leone et al., 1994), repeated rrTMS is a relatively safe technique in healthy normal subjects. As rrTMS allows disruption of cortical function for a longer period, it has the potential of becoming a particularly useful tool for the study of cognitive function as well as sensory or motor function.     

The influence of DNA glycosylases on spontaneous mutation

In the present study we examined the effects of phasic activation of the nucleus locus coeruleus (LC) on transmission of somatosensory information to the rat cerebral cortex. The rationale for this investigation was based on earlier findings that local microiontophoretic application of the putative LC transmitter, norepinephrine (NE), had facilitating actions on cortical neuronal responses to excitatory and inhibitory synaptic stimuli and more recent microdialysis experiments that have demonstrated increases in cortical levels of NE following phasic or tonic activation of LC. Glass micropipets were used to record the extracellular activity of single neurons in the somatosensory cortex of halothane-anesthetized rats. Somatosensory afferent pathways were activated by threshold level mechanical stimulation of the glabrous skin on the contralateral forepaw. Poststimulus time histograms were used to quantitate cortical neuronal responses before and at various time intervals after preconditioning burst activation of the ipsilateral LC. Excitatory and postexcitatory inhibitory responses to forepaw stimulation were enhanced when preceded by phasic activation of LC at conditioning intervals of 200-500 ms. These effects were anatomically specific in that they were only observed upon stimulation of brainstem sites close to (>150 micron) or within LC and were pharmacologically specific in that they were not consistently observed in animals where the LC-NE system had been disrupted by 6-OHDA pretreatment. Overall, these data suggest that following phasic activation of the LC efferent system, the efficacy of signal transmission through sensory networks in mammalian brain is enhanced.     

A case of cortical reflex positive-negative myoclonus--electrophysiological study

An 11-year-old girl who had the positive-negative myoclonus and the history of the generalized tonic clonic seizure was electrophysiologically studied. She had no siblings with either myoclonus or epilepsy, and her intellectual level was normal. She had no other neurological deficits including ataxia, pyramidal and extrapyramidal signs. Surface EMG showed a brief increase in the EMG activity followed by the silent period associated with positive and negative myoclonus during sustained wrist extension. Giant SEP and C reflex (38.6 ms) following electric stimulation of the median nerve at the wrist were obtained in the resting condition and the silent period (about 180 ms) following C reflex was obtained during voluntary contraction. Jerk-locked back averaging of the EEG time-locked to the onset of the myoclonic discharge recorded from the right biceps muscle showed a cortical spike at the left central region preceding the myoclonus onset by 12.6 ms. The latency of C reflex in this case was very short compared with that of previously reported cortical reflex myoclonus. The estimated cortical delay between the arrival of the somatosensory volley and the motor cortex discharge responsible for the C reflex was -1.0 ms and this value was shorter than that in patients with typical cortical reflex myoclonus (mean 3.7 +/- 1.1 ms). Conditioning stimuli (C) of the right median nerve at the wrist started to facilitate the amplitude of the motor evoked potential recorded from the right abductor pollicis brevis muscle after magnetic test stimuli (T) of the left motor cortex at 20 ms of the C-T interval. This C-T interval was shorter than that (24.6 +/- 1.6 ms) in patients with the typical cortical myoclonus. These electrophysiological findings suggested the shorter reflex pathway of the cortical reflex myoclonus in this case than in typical cortical reflex myoclonus. We speculated that the myoclonus was based upon the direct sensory projection from the thalamus to the motor cortex in this case.     

Increase of 5-HT7 (serotonin-7) and 5-HT1A (serotonin-1A) receptor mRNA expression in rat hippocampus after adrenalectomy

Kinematic and electromyographic (EMG) analysis of a target-directed, maximal velocity movement was used to investigate the effects of high-force eccentric exercise on the neuromuscular control of elbow flexion. Ten non-weight-trained females [19.6 (1.6) years old] performed 50 maximal velocity elbow flexion movements from 0 to 1.58 rad (90 degrees), as rapidly as possible in response to a light stimulus, while kinematic and triphasic EMG parameters were measured. This was done three times pre-exercise, immediately and 1, 2, 3, 4, and 5 days following the 50 maximal eccentric elbow flexion actions. The eccentric exercise caused lengthening of kinematic parameters including total movement time and time to peak velocity. The EMG elements of the biceps brachii (b.) motor time, time to peak EMG, biceps b. burst duration, and the latency period between biceps b. and triceps b. bursts were lengthened post-exercise. These changes persisted for up to 5 days post-exercise. The exercise also caused a large increase in serum creatine kinase (CK) activity. It was concluded that high-force eccentric exercise in this population caused prolonged changes in neuromuscular control that were a function of exercise-induced disruption of the skeletal muscle. Compensation in the central motor program was such that the components of the triphasic EMG pattern were systematically lengthened.     

Effects of regional striatal lesions on motor, motivational, and executive aspects of progressive-ratio performance in rats.

The striatum is implicated in response selection and performance, the dorsal striatum in sensorimotor control and habit learning, and the ventral striatum in motivation and rewarded behaviors. Ventral striatal lesions produce performance changes on food-reinforced, progressive-ratio (PR) schedules, but the effects of dorsal striatal lesions on this task are not known. In this study, neither medial nor lateral dorsal striatal lesions produced deficits on the main motivational indices of PR performance. In contrast, significant impairments were observed in motoric or "executive" aspects of performance. Motivationally related manipulations of the task (food deprivation and reward magnitude) produced some subtle lesion-specific changes in behavior on these motoric or executive aspects of performance. Findings are discussed in relation to the roles of the dorsal and ventral striatum in reward-related behaviors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)